This study will attempt to define the proteolytic enzymes involved in connective tissue resorption in human skin. We will isolate, characterize and produce antibodies to collagenase, Cathepsin D, Cathepsin B, neutral proteinase, or any other proteinase of interest in human skin. Using immunocytochemical techniques, we will localize the cells responsible for proteinase production. The role of these specific enzymes in catabolism in general, and connective tissue resorption specifically, will be evaluated by; 1. incubating enzyme depleted skin with purified proteinases and defining which component of the tissue is degraded, 2. adding the enzyme to autolyzing tissue and measuring which component of the tissue demonstrates facilitated degradation, 3. inhibiting specific enzymes with antisera in tissues undergoing autolytic degradation and evaluating inhibition of catabolism of specific connective tissue components and 4. inhibiting connective tissue resorption in tissue cultures of skin by the use of specific antisera. We will investigate the role of proteinases in clinical disease by studying skin biopsies from patients with selected diseases, such as Lupus Erythematosus, for amounts of given proteinases, immunocytological localization and distribution of proteinases, and lysosomal stability. These studies should provide insight into the pathophysiological role of these enzymes in connective tissue catabolism and could allow us to design specific inhibitors for relevant proteinases so tissue destruction would be prevented.